کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904798 | 1086696 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Autocrine regulation of human urothelial cell proliferation and migration during regenerative responses in vitro
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کلمات کلیدی
Tgf-α12-O-tetradecanoylphorbol 13-acetateEGFRPI3-kinaseBTCERKtPABPEEpiregulinHB-EGFEGFMAPK - MAPKamphiregulin - آمفیرگولینWound Healing - التیام زخمHER - اوRegeneration - باززاییBetacellulin - بتاکولولینtransforming growth factor alpha - تبدیل فاکتور رشد آلفاProliferation - ترویجEPR - تشدید پارامغناطیس الکترونepidermal growth factor - عامل رشد اپیدرمیHeparin-binding epidermal growth factor - عامل رشد اپیدرمی اتصال هپارینbovine pituitary extract - عصاره هیپوفیز گاوPhosphatidyl Inositol 3-kinase - فسفاتیدیل آنزیم 3-کینازBladder - مثانهMEK - مجاهدین خلقMigration - مهاجرتmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenmitogen-activated protein kinase kinase - پروتئین کیناز کیناز فعال Mitogen فعالextracellular regulated kinase - کیناز تنظیم شده خارج سلولیhuman epidermal growth factor receptor - گیرنده عامل فاکتور رشد اپیدرمی انسانEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمالUrothelium - یوروتلیوم یا بافت مثانه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Regeneration of the urothelium is rapid and effective in order to maintain a barrier to urine following tissue injury. Whereas normal human urothelial (NHU) cells are mitotically quiescent and G0 arrested in situ, they rapidly enter the cell cycle upon seeding in primary culture and show reversible growth arrest at confluency. We have used this as a model to investigate the role of EGF receptor signaling in urothelial regeneration and wound-healing. Transcripts for HER-1, HER-2, and HER-3 were expressed by quiescent human urothelium in situ. Expression of HER-1 was upregulated in proliferating cultures, whereas HER-2 and HER-3 were more associated with a growth-arrested phenotype. NHU cells could be propagated in the absence of exogenous EGF, but autocrine signaling through HER-1 via the MAPK and PI3-kinase pathways was essential for proliferation and migration during urothelial wound repair. HB-EGF was expressed by urothelium in situ and HB-EGF, epiregulin, TGF-α, and amphiregulin were expressed by proliferating NHU cells. Urothelial wound repair in vitro was attenuated by neutralizing antibodies against HER-1 ligands, particularly amphiregulin. By contrast, the same ligands applied exogenously promoted migration, but inhibited proliferation, implying that HER-1 ligands provoke differential effects in NHU cells depending upon whether they are presented as soluble or juxtacrine ligands. We conclude that proliferation and migration during wound healing in NHU cells are mediated through an EGFR autocrine signalling loop and our results implicate amphiregulin as a key mediator.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 306, Issue 1, 15 May 2005, Pages 216-229
Journal: Experimental Cell Research - Volume 306, Issue 1, 15 May 2005, Pages 216-229
نویسندگان
Claire Varley, Gemma Hill, Stephanie Pellegrin, Nicola J. Shaw, Peter J. Selby, Ludwik K. Trejdosiewicz, Jennifer Southgate,